Cyanoethylation of hydroxy compounds

ABSTRACT

LONG CHAIN FATTY ACID DERIVATIES CONTAINING AT LEAST ONE HYDROXYL GROUP PER MOLECULE ARE CYANOETHYLATED BY DISSOLVING THEM INACRYLONITRILE AND ADDING A STRONG BASE TO CATALYZE THE REACTION BETWEEN THE FATTY ACID DERIVATIVE AND THE ACRYLONITRILE TO PROVIDE A B-CYANOETHYLATED PRODUCT. THE ACRYLONITRILE FUNCTIONS BOTH AS A SOLVENT AND AS A REACTANT. A NON-EXLUSIVE, IRREVOCABLE, ROYALTY-FREE LICENSE IN THE INVENTION HEREIN DESCRIBED, THROUGHOUT THE WORLD FOR ALL PURPOSES OF THE UNITED STATES GOVERNMENT, WITH THE POWER TO GRANT SUBLICENSES FOR THE PURPOSES, IS HEREBY GRANTED TO HE GOVERNMENT OF THE UNITED STATES OF AMERICA.

United States Patent 3,701,802 CYANOETHYLATION 0F HYDROXY COMPOUNDS Gerhard Maerker, Oreland, and Harold E. Kenney,

Jenkintown, Pa., assignors to the United States of America as represented by the Secretary of Agriculture No Drawing. Continuation-impart of application Ser. No. 594,252, Nov. 14, 1966. This application Aug. 22, 1969, Ser. No. 852,469

Int. Cl. C09f 7/00 US. Cl. 260-404 8 Claims ABSTRACT OF THE DISCLOSURE This application is a continuation-in-part of our copending application for patent, Ser. No. 594,252 filed Nov. 14, 1966, now abandoned.

This invention relates to the cyanoethylation of hydroxy compounds and more particularly to a process whereby organic compounds containing one or more hydroxy groups may be effectively converted to valuable B-cyanoethyl ethers. It comprises reacting an unsaturated organic nitrile, used both as solvent and as reactant, with a hy-- droxy compound in the presence of a strong base, whereby the p-cyanoethyl ethers are obtained.

Heretofore cyanoethylations have been carried out by dissolving hydroxylated materials and a strong base in an inert or non-participating solvent and adding the required amount of acrylonitrile to this solution. Application of this method to certain hydroxy compounds, particularly hydroxylated long chain fatty esters, results in low yields of the desired products and leads to the formulation of byproducts which are difiicult to remove.

Previous workers have found that acrylonitrile polymerizes violently in the presence of concentrated alkali, and their recommendations preclude the addition of strong base to acrylonitrile. It was therefore totally unexpected that acrylonitrile could be used as solvent in cyanoethylations, as has now been found, and that such use permitted the cyanoethylation in high yields of compounds which heretofore had resisted cyanoethylation.

It is an object of this invention to provide a method of cyanoethylating long chain fatty acid derivatives in which the long chain hydrocarbon moiety contains at least one hydroxyl attached to a primary, secondary or tertiary carbon atom.

It is a further object of this invention to cyanoethylate long chain fatty acid derivatives by a process in which acrylonitrile is used as both reactant and solvent.

It is a still further object of this invention to cyanoethylate long chain fatty acid derivatives by a process heretofore considered highly dangerous and inadvisable, that is, by the addition of a strong base to a large excess of acrylonitrile in which the fatty acid derivative is'dissolved.

In general, according to this invention the above ob- 3,701,802 Patented Oct. 31, 1972 ice jects are accomplished by dissolving a long chain fatty acid derivative containing at least one hydroxyl group per molecule in an amount of acrylonitrile sufficient to react with and to dissolve the fatty acid derivative, adding a catalytic amount of a strong base to the acryloni: trile solution, and recovering a fi-cyaruoethylated product from the reaction mixture.

The hydroxy compounds which are most conveniently prepared, handled and cyanoethylated in accordance with the principles of our invention contain at least one hydroxy group per molecule. The hydroxy group can be attached to a primary, secondary or tertiary carbon atom and can be a substituent on a carbon atom which is part of an aliphatic alicyclic, heterocyclic or alkylaromatic compound.

The hydroxy compound which can be cyanoethylated by the process of our invention may contain other nonreactive functional groups or substituents. Such functional groups or substituents may be ester, cyano, nitro, amido, halide, formyl, ether, epoxy and other functions. The hydroxy compound can also contain reactive functional groups each of which may, for the purpose of this invention, be considered to react in an analogous manner as an additional hydroxy group. Such reactive functional groups include mercapto, amino, imino, epimino, keto, activated methylene and other functional groups which are known to undergo cyanoethylation. The hydroxy compound can be saturated or unsaturated and can contain one or more hydroxy groups. If the hydroxy group is a substituent in a compound also containing a carboxylic ester function, the ester may have resulted from the combination of a monoor polyfunctional carboxylic acid with a monoor polyhydric alcohol, and the hydroxy function can be substituent in either the acid portion or the alcohol portion of the ester function.

The strong base which is utilized by our process in the cyanoethylation of hydroxy compounds can be any base effective in aiding in the removal of protons from hydroxy groups. Such bases include alkali metal oxides, hydroxides, alkoxides or amides, quaternary ammonium hydroxides, alkali metal salts of alkyl carbanions and the like. Preferred are alkali metal hydroxides such as sodium or potassium hydroxide or quaternary ammonium hydroxides such as benzyltrimethylammonium hydroxide.

The acrylonitrile to be used in carrying out our invention may be of any suitable purity grade and may contain an inhibitor, if desired, to limit autopolymerization of the unsaturated nitrile. If desired, the acrylonitrile may be distilled or otherwise purified to remove stabilizers or polymerization inhibitors, with the result that the ensuing cyanoethylation reaction as practiced by the process of our invention will be more vigorous than it would be were the stabilizer or inhibitor still present.

Our invention may be practiced in a wide variety of manners depending on the specific hydroxy compound to be treated, on the nature of the fl-cyanoethyl ethers produced, on the particular base employed and on the particular operating conditions chosen. In accordance with a preferred mode of operation the hydroxy compound is dissolved in acrylonitrile, or if desired, in a mixed solvent consisting of acrylonitrile and a non-reactive solvent used as diluent. The employment of a non-reactive co-solvent is convenient in many cases, but it is not essential to the operation of our process. Co-solvents which may be chosen, if desired, include benzene, toluene, xylene, pentane, hexane, cyclohexane, heptane, acetone, methyl ethyl ketone, ether, carbon tetrachloride, chloroform, methylene chloride, acetonitrile, nitromethane, nitrobenzene, chlorobenzene, tetrahydrofuran, 1,4-dioxane, dimethyl formamide, dimethyl sulfoxide, bis-(2- methoxyethyl) ether, ethyl acetate, amyl acetate, methyl acetate, l-methyl-Z-pyrolidinone, pyridine, quinoline or 3 any other non-aqueous, non-reactive compound which is suitable. Particularly preferred oo-solvents are low-boiling, non-reactive polar solvents such as acetone, dioxane, methyl acetate, dimethyl sulfoxide, pyridine and the like.

In further execution of our preferred method the solution of the hydroxy compound is introduced into a suitable reaction vessel which may be provided with means for agitation of the reaction mixture, if desired. The base is then added to the hydroxy compound solution with external heating or cooling, as the operator wishes.

The base used in carrying out the process of our invention may be added as a powder, as a slurry, or as a solution in a suitable solvent. We prefer to add the base in the form of an aqueous or non-aqueous solution, the concentration of which may be varied between 10% and 100%. If an aqueous solution of the base is employed, the preferred range of concentration is between 20% and 70%. In many cases, as for instance when a quaternary ammonium hydroxide is the base utilized, best results are obtained if the concentrations of the base in water or alcohols are in. the 25% to 55% range.

The formation of one fl-cyanoethoxy group consumes one molecule of acrylonitrile. A molar equivalent of acrylonitrile for each hydroxy group present in the hydroxy compound to be cyanoethylated is therefore the minimum amount which is consistent with the achievement of high yields of B-cyanoethyl ether. Since, however, the preferred execution of the process of our invention utilizes acrylonitrile as solvent, either alone or in conjunction with co-solvent, the amount of acrylonitrile employed generally exceeds the stoichiometrically required amount. The total amount of acrylonitrile used in the preferred operation of our process varies with the solubility requirements of the hydroxy compound treated and with the experimental conditions employed.

We prefer to carry out our invention in a temperature range of from about 5 C. to about 100 C. We particularly prefer to maintain the reaction mixture at a temperature range of from C. to 30 C. during the addition of the base. Since the cyanoethylation reaction as practiced by the process of our invention is often exothermic, the heat evolved by the reaction mixture subsequent to the mixing. of the reagents and base may be removed by any suitable means. We prefer to practice our invention by regulating the temperature of our reaction mixture within the preferred range by external addition of removal of heat as required.

When the hydroxy compound is treated by our method with an excess amount of acrylonitrile and with base, only a brief reaction period is required. The exact length of this period varies with the particular hydroxy compound, the type and amount of the specific co-solvent chosen, the amount, concentration and nature of the base used, the amount of inhibitor present, and the reaction temperature employed. Even though long reaction times may be used without altering the results, brief reaction periods are preferred.

After the cyanoethylation reaction has reached completion, as judged from the fact that the hydroxy content of the mixture has reached a low and constant level or has disappeared, the product may be isolated by any means suitable to the operator. For example, the base and any byproducts of the reaction may be removed by extraction, distillation, adsorption, ion exchange, crystallization, sublimation and the like. In carrying out our invention we prefer to dilute the reaction mixture with acidified water, extract the desired product from the mixture with a solvent which is poorly miscible with water, wash and dry the solution containing the product and then distill this solution to isolate the anhydrous product.

The following examples are presented to illustrate the practice of the present invention and are not to be considered as limitations thereof.

4 EXAMPLE 1 Methyl threo-9,IO-dihydroxystearate (5.0 g.; 0.015 mole) was placed in a 500 ml. round bottom flask and dissolved in 40 ml. (0.60 mole) acrylonitrile (mole ratio of 1:40, respectively). To this solution was added, rapidly with stirring, 1 ml. of a 40% aqueous solution of benzyltrimethylammonium hydroxide. The temperature of the reaction mixture rose rapidly to reflux after the addition of the base. The mixture was agitated for one hour while it cooled to room temperature. The mixture was then diluted with 50 ml. of water after which 100 ml. of acetone was added. The resulting mixture was neutralized with dilute aqueous HCl and extracted with three 200 ml. portions of ether. The combined extracts were washed with water, dried over sodium sulfate and evaporated to a residue weight of 6.6 g. Infrared analysis of the residue demonstrated the presence of nitrile, ester and ether absorption bands and the absence of hydroxy bands. Elemental, G.L.C. and -N.M.R. analysis confirmed that the residue was predominantly methyl 9,l0-bis(2-cyanoethoxy)-stearate.

EXAMPLE 2 To 2.0 g. (0.006 mole) methyl erythro-9,10-dihydroxystearate dissolved in 15 ml. (0.27 mole) acrylonitrile (mole ratio of 1:45, respectively) was added, rapidly with stirring 0.4 ml. of a 40% aqueous solution of benzyltrimethylamrnonium hydroxide. The solution rapidly reached reflux temperature, was allowed to cool to 30 C. and was stirred at that temperature for three hours. The reaction mixture was worked up as described in Example 1 to obtain 2.6 g. of product which contained 97% of the dicyanoethoxy addition product.

EXAMPLE 3 1.0 g. (0.0029 mole) of the dihydroxy ester obtained from the hydration of methyl 9,l0,12,13-diepoxystearate was dissolved in 5 ml. (0.075 mole) acrylonitrile and then 0.2 ml. of the 40% aqueous solution of benzyltrimethylammonium hydroxide was added rapidly with stirring. After the initial reaction subsided, the reaction mixture was stirred three hours at room temperature, allowed to stand overnight and then worked up as described in Example 1 to obtain 1.3 g. of product. Thin-layer chromatography and infrared spectroscopy showed that the product had one principal component which contained a-cyanoethyoxy groups and no hydroxy functions.

EXAMPLE 4 To a solution of 0.12 g. (0.0004 mole) 1,9,10-trihydroxyoctadecane in 1 ml. (0.015) acrylonitrile (mole ratio of 1:375.5, respectively) was added 0.1 ml. of a 40% aqueous solution of benzyltrimethylammonium hydroxide. After the initial reaction subsided, the mixture was stirred at room temperature for one hour. The reaction mixture was worked up as described in Example 1 to obtain 0.174 g. of product consisting of 60% of the tricyanoethoxy derivative and 40% of the diaddition product. The infrared spectrum of the product was consistent with the indicated composition.

EXAMPLE 5 To a solution of 1.0 g. (0.003 mole) methyl 9,10,12- trihydroxystearate in 15 ml. (0.27 mole) acrylonitrile (mole ratio of 1:90, respectively) was added, rapidly with stirring, 0.6 ml. of a 40% aqueous solution of benzyltrimethylammonium hydroxide. After the initial reaction subsided, the reaction mixture was stirred for three hours at room temperature and was then worked up as described in Example 1 to obtain 1.4 g. product. TLC analysis indicated that of the product was the desired tri-flcyanoethoxy derivative.

EXAMPLE 6 To a solution of 1.1 g. (0.0035 mole) methyl 12-hydroxystearate in 5 ml. (0.075 mole) acrylonitrile (mole ratio of 1:21.4, respectively) was added, rapidly with stirring, 0.2 ml. of a 40% aqueous solution of benzyltrimethylammonium hydroxide. After the initial reaction subsided, the mixture was stirred for three hours at room temperature and then allowed to stand overnight. The mixture was worked up as described in Example 1 to obtain 1.4 g. product. Ninety-five percent of the product was the desired fi-cyanoethoxy derivative.

EXAMPLE 7 To a solution of 0.25 g. hydrated epoxidized soybean oil (7.3% OH) in ml. acrylonitrile was added, rapidly with stirring, 0.2 ml. of a 40% aqueous solution of benzyltrimethylammonium hydroxide. After the initial reaction had subsided the mixture was stirred three hours at room temperature and then worked up as described in Example 1 to obtain 0.50 g. of product. The latter had strong nitrile absorption in the infrared and contained less than of the original hydroxy content.

EXAMPLE 8 EXAMPLE 9 To a solution of 0.5 g. (0.0015 mole) methyl 12-hydroxystearate in 3 ml. (0.045 mole) acrylonitrile (mole ratio of 1:30, respectively) was added, rapidly with stirring, a solution of 0.1 g. KOH in 1 ml. 90% aqueous tert-butanol. The reactionmixture was stirred for one hour at room temperature and then worked up as described in Example 1 to obtain 06 g. product. GLC analysis indicated that 78% of the product was the B- cyanoethoxy derivative.

EXAMPLE 10 To a solution of 0.5 g. (0.0015 mole) methyl l2-hydroxystearate in 3 ml. (0.045 mole) acrylonitrile (mole ratio of 1:30, respectively) was added, rapidly with stirring, a solution of 0.1 g. KOH in 1 ml. methyl alcohol. After the initial reaction subsided the mixture was stirred for one hour at room temperature and then worked up as described in Example 1 to obtain 0.5 g. product. GLC analysis indicated that the desired B-cyanoethoxy derivative was the predominant component of the product.

EXAMPLE 11 To a solution of 1.0 g. (0.003 mole) of methyl 12- hydroxystearate in 5 ml. (0.075 mole) acrylonitrile (mole ratio of 1:25, respectively) was added, rapidly with stirring, a solution of 0.1 g. NaOH in 1 ml. water. The reaction mixture was heated at the reflux temperature for 15 minutes and then worked up as described in Example 1 to obtain 1.2 g. product. GLC analysis indicated the presence of a significant amount of the desired {3- cyanoethoxy derivative.

EXAMPLE 12 To a slurry of 0.5 g. (0.0015 mole) methyl l2-hydroxystearate in 5 ml. (0.075 mole) acrylonitrile (mole ratio of 1:50, respectively) at 15 C., was added, 0.1 ml. 40% aqueous solution of benzyltrimethylammonium hydroxide. The heat of reaction warmed the solution so that all solids were dissolved. The reaction mixture was stirred for one hour at 15 C., and then worked up as described in Example 1 to obtain 0.55 g. product. GLC analysis indicated that 95% of the product was the e-cyanoethoxy derivative.

EXAMPLE 13 To a solution of 0.5 g. (0.0015 mole) methyl l2-hydroxystearate in 5 ml. (0.075 mole) acrylonitrile (mole ratio of 1:50, respectively) at 60 C. was added, rapidly with stirring, 0.1 ml. 40% aqueous solution of benzyltrimethylammonium hydroxide. The reaction mixture was stirred for one hour at 60 C. and then worked up as described in Example 1 to obtain 0.50 g. product. GLC analysis indicated that 51% of the product was the fi-cyanoethoxy derivative.

In addition to the above examples, other experiments were run that show the eifect of variations of temperature, amount of catalyst, diluents, and inhibitors on the reaction process.

Methyl l2-hydroxystearate was cyanoethylated at various temperatures in the range of 15 to 60 C. The degree of cyanoethylation was largest (94.2%) at 15 C. and gradually decreased to 51.4% as the reaction temperature increased to 60 C. The induction period, that is, the time between the addition of catalyst and the initiation of polymerization of acrylonitrile, varied from 129 seconds at 15 C. to less than 1 second at 60 C. These results are shown in Table I.

Variations in the amount of catalyst affected both the degree of cyanoethylation and the amount of insoluble polymer as shown in Table II. At low catalyst concentration very little reaction took place. At higher mole ratios the degree of cyanoethylation was between 76.7 and 97.2% and the amount of insoluble polymer formed varied from 0.40 to 1.40 gm. At high mole ratios the induction period increased considerably. This was probably caused by the inhibiting eifect of the water added with the catalyst.

The addition of 2% by volume of water and 2% concentrated aqueous ammonia inhibited the induction period by from 4 to 10 minutes, respectively, but the yield of product was the same for both (93%) as the yield without an inhibitor.

Dilution of the acrylonitrile with pyridine and with 1,4-dioxane from a ratio of 10/1 to a ratio of 1/1 decreased the degree of cyanoethylation from 86.0% to 39.0% indicating that it is important to keep the amount of co-solvent to a minimum.

These results show that cyanoethylation is more than completed during the induction period under the proper conditions of temperature and amounts of catalyst and diluent and that the ideal procedure is to isolate the product immediately at the end of the induction period. In this way polymerization of acrylonitrile is kept to a minimum. However, this procedure was not followed in the examples cited previously in this specification. In most of the examples, the reaction mixture was stirred from 0.5 hour to 3 hours after the induction period in an attempt to increase the yield.

TABLE 1.CYANOETHYLA'IION OF METHYL 12-HY- DROXYSTEARATE. EFFECT OF VARIATION IN REAC- TION TEMPERATURE Product Degree Insoluble Inducot eyanopolymer tion Weight, ethylaweight, period, Temperature g. tion 1 g. sec,

1 Starting mixture: 0.5 g. methyl 12-hydroxystearate, 4.0 g. acrylonitrile, 0.1 ml. BTAH solution.

1 Percentage of recovered, cyanoethylated starting material, as measured by GLC.

TABLE II.CYANOETHYLATION OF METHYL 12-HY- DROXYSTEARATE. EFFECT OF VARIATION IN THE AMOUNT OF CATALYST l Benzyltrlmethylammonlum hydroxide as 40% aqueous solution.

I Starting mixture: 0.5 g. methyl 12-hydroxystearate, 4.0 g. acrylonitrile, catalyst as specified, temp. 26

' atio: moles of methy 12-hydroxystearatelmoles of catalyst.

4 Percentage of recovered, cyanoethylated starting material, as measured by GLO.

We claim:

1. In a process for cyanoethylating a long chain fatty acid ester in which the long chain hydrocarbon moiety contains 18 carbon atoms and from 1 to 3 hydroxyl groups attached to a member of the group consisting of primary, secondary and tertiary carbon atoms, the improvement which consists essentially of dissolving the fatty acid ester in an amount of acrylonitrile suflicient to react with and to dissolve said fatty acid ester, adding to said solution in a rapid and unitary manner a catalytic amount of a strong base selected from the group consisting of alkali metal hydroxides and quaternary ammonium hydroxides, reacting at a temperature between 5 and 100 C. for from about 15 minutes to about 3 hours, and recovering a p-cyanoethylated product from the reaction mixture.

2. The process of claim 1 wherein the fatty acid derivative and acrylonitrile are present in molar ratios from about 1:21.4 to l:1071.4, respectively.

3. The process of claim 2 in which the fatty acid derivative contains one hydroxy group-per molecule.

4. The process of claim 3 in which the fatty acid derivative is methyl 12-hydroxystearate.

5. The process of claim 2 in which the fatty derivative contains two hydroxy groups per molecule.

6. The process of claim 5 in which the fatty derivative is methyl three-9,10-dihydroxystearate.

7. The process of claim 5 in which the fatty derivative is methyl erythro-9,l0 dihydroxystearate.

8. The process of claim 2 in which the fatty acid derivative contains three hydroxy groups per molecule.

acid

acid

acid

References Cited UNITED STATES PATENTS 2,983,738 5/1961 Stenberg 260-404 2,495,214 1/ 1950 Crews 260-404 FOREIGN PATENTS 170,489 5/1965 U.S.S.R. 260465.6

451,809 10/1948 Canada 260-465.6

OTHER REFERENCES Maerker et al., Cyanoethylation of Hydroxy Ders. of Fats (1968) I.A.O.C.S. 45, pp. 72-75.

LEWIS GO'ITS, Primary Examiner G. HOLLRAH, Assistant Examiner US. Cl. X.R. 

